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21.
He L Zhang Z Yu Y Ahmed S Cheung NS Qi RZ 《Cellular and molecular life sciences : CMLS》2011,68(9):1633-1643
The neuronal Cdk5 activator p35 is involved in a multitude of neuronal activities, including cytoskeletal organization. We
show here that p35 directly interacts with filamentous actin (F-actin) but not with monomeric actin (G-actin). Through binding,
p35 induces the formation of actin bundles and stabilizes F-actin against dilution-induced depolymerization. p35 forms intermolecular
self-associations, suggesting that p35 cross-links actin filaments into bundles via its intermolecular self-association. p35
dimerization and association with F-actin occur at the N-terminal region that is absent in the calpain-cleaved product p25,
indicating that such p35 properties are lost by its truncation induced under neurotoxic conditions. Using p35 phosphorylated
by Cdk5 and a mutational approach, we demonstrate that the phosphorylation of p35 promotes its homodimerization and p35-induced
formation of F-actin bundles. In addition, the phosphorylation regulates p35 distribution to microtubule and actin cytoskeletons.
Together, these observations define a novel function for p35 in cytoskeletal regulation. 相似文献
22.
This paper presents a dynamic probabilistic marking algorithm with multiple routing address tags, which allows the victim to traceback the origin of ICMP (Internet Control Message Protocol)-based direct and reflective DoS attacks. The proposed approach makes full use of scalable data space of ICMP packet to achieve multiple information tags. The difference between this proposal and previous proposals lies in two points. First, the number of packets needed by the victim to reconstruct the attack path is greatly reduced because of three key mechanisms: multi-tag, uniform leftover probability, and tag location choice based on the module of accommodated tag numbers within a packet. Second, the true origin of both direct and reflective ICMP-based DoS attacks can be traced. 相似文献
23.
Ahmed H.Zewail Christopher King Daniel Hook David Pendlebury James Wilsdon Jonathan Adams 《科学观察》2011,(5):21-29
Thomson Reuters 发布的全球系列研究报告表明,以阿拉伯、伊朗、土耳其为主的中东国家的科学研究与西文国家相比落后许多.当然,也有部分中东的科学家或研究机构从事着世界一流的研究工作.事实上,论文数量及引文指标都清晰地表明,近10年中东地区的研究工作有了很大的进步,表现出了鼓舞人心的发展趋势. 相似文献
24.
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day CL Kaufmann DE Kiepiela P Brown JA Moodley ES Reddy S Mackey EW Miller JD Leslie AJ DePierres C Mncube Z Duraiswamy J Zhu B Eichbaum Q Altfeld M Wherry EJ Coovadia HM Goulder PJ Klenerman P Ahmed R Freeman GJ Walker BD 《Nature》2006,443(7109):350-354
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. 相似文献
25.
Barber DL Wherry EJ Masopust D Zhu B Allison JP Sharpe AH Freeman GJ Ahmed R 《Nature》2006,439(7077):682-687
Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question, we analysed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8 T cells. Here we report that PD-1 (programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 (also known as B7-H1), enhanced T-cell responses. Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. Blockade of the CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) inhibitory pathway had no effect on either T-cell function or viral control. These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections. 相似文献
26.
Abazov VM Abbott B Abdesselam A Abolins M Abramov V Acharya BS Adams DL Adams M Ahmed SN Alexeev GD Alton A Alves GA Arnoud Y Avila C Babintsev VV Babukhadia L Bacon TC Baden A Baffioni S Baldin B Balm PW Banerjee S Barberis E Baringer P Barreto J Bartlett JF Bassler U Bauer D Bean A Beaudette F Begel M Belyaev A Beri SB Bernardi G Bertram I Besson A Beuselinck R Bezzubov VA Bhat PC Bhatnagar V Bhattacharjee M Blazey G Blekman F Blessing S Boehnlein A Bojko NI Bolton TA Borcherding F Bos K 《Nature》2004,429(6992):638-642
The standard model of particle physics contains parameters--such as particle masses--whose origins are still unknown and which cannot be predicted, but whose values are constrained through their interactions. In particular, the masses of the top quark (M(t)) and W boson (M(W)) constrain the mass of the long-hypothesized, but thus far not observed, Higgs boson. A precise measurement of M(t) can therefore indicate where to look for the Higgs, and indeed whether the hypothesis of a standard model Higgs is consistent with experimental data. As top quarks are produced in pairs and decay in only about 10(-24) s into various final states, reconstructing their masses from their decay products is very challenging. Here we report a technique that extracts more information from each top-quark event and yields a greatly improved precision (of +/- 5.3 GeV/c2) when compared to previous measurements. When our new result is combined with our published measurement in a complementary decay mode and with the only other measurements available, the new world average for M(t) becomes 178.0 +/- 4.3 GeV/c2. As a result, the most likely Higgs mass increases from the experimentally excluded value of 96 to 117 GeV/c2, which is beyond current experimental sensitivity. The upper limit on the Higgs mass at the 95% confidence level is raised from 219 to 251 GeV/c2. 相似文献
27.
28.
ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles 总被引:13,自引:0,他引:13
Renwick A Thompson D Seal S Kelly P Chagtai T Ahmed M North B Jayatilake H Barfoot R Spanova K McGuffog L Evans DG Eccles D;Breast Cancer Susceptibility Collaboration 《Nature genetics》2006,38(8):873-875
We screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and two in controls (P = 0.0047). The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.) = 1.51-3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer. 相似文献
29.
30.
Ahmed ZM Masmoudi S Kalay E Belyantseva IA Mosrati MA Collin RW Riazuddin S Hmani-Aifa M Venselaar H Kawar MN Tlili A van der Zwaag B Khan SY Ayadi L Riazuddin SA Morell RJ Griffith AJ Charfedine I Caylan R Oostrik J Karaguzel A Ghorbel A Riazuddin S Friedman TB Ayadi H Kremer H 《Nature genetics》2008,40(11):1335-1340